Intraocular neutralizing antibodies against aflibercept in patients with age related macular degeneration

Gyenes, Andrea; István, Lilla; Benyó, Fruzsina; Papp, András; Resch, Miklós; Sándor, Noémi; Józsi, Mihály; Nagy, Zoltán Zsolt; Kovács, Illés; Kiss, Szilárd

doi:10.1186/s12886-022-02761-9

Cited by 2 publications

(1 citation statement)

References 50 publications

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“…In an animal model of retinitis pigmentosa, intravitreal administration of AAV was capable of transducing Muller cells, photoreceptors, and RPE secondary to the hypothesized increased permeability and disorganization of the ILM [31]. For AMD specifically, the blood-retinal barrier may be impaired changing the intraocular immune response [32].…”

Section: Key Pointsmentioning

confidence: 99%

Gene therapy for age-related macular degeneration: potential, feasibility, and pitfalls

Berkowitz,

Finn

2024

Current Opinion in Ophthalmology

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Purpose of review The landscape for age-related macular degeneration (AMD) is rapidly changing with addition of biosimilars and now United States Food and Drug Administration (FDA) approved nonneovascular AMD (nnAMD) treatment options. These developments have inspired a burgeoning pipeline of gene therapy approaches focused on similar antivascular endothelial growth factors (VEGF) and complement related pathways. Historic and more recent setbacks in the gene therapy pipeline, including intraocular inflammatory reactions, have raised important concerns for adverse events related to AMD therapeutics both for gene and nongene approaches. The specific clinical profile of these therapeutics approaching later stage clinical trials are complex and under active investigation; however, these options hold promise to disrupt the current landscape and change management paradigms for one of the leading causes of vision loss worldwide. Recent findings This review covers current gene therapy approaches for neovascular AMD (nAMD) and nnAMD. Intravitreal, suprachoroidal, and subretinal delivery routes are discussed with attention to technical procedure, capabilities for transgene delivery to target tissue, immunogenicity, and collateral effects. Suprachoroidal delivery is an emerging approach which may bridge some of the practical drawbacks for intravitreal and subretinal methods, though with less elaborated immunologic profile. In parallel to delivery modification, viral vectors have been cultivated to target specific cells, with promising enhancements in adeno-associated viral (AAV) vectors and persistent interest in alternate viral and nonviral delivery vectors. Ongoing questions such as steroid or immunosuppressive regimen and economic considerations from a payer and societal perspective are discussed. Summary The present review discusses emerging gene therapy options which could foster new, more durable nAMD and nnAMD therapeutics. These options will need refinement with regards to route, vector, and dosage, and specialists must decipher the specific clinical risk benefit profile for individual patients. Ongoing concerns for immunogenicity or dosage related adverse events could stifle progress, while further vector development and refined delivery techniques have the potential to change the safety and efficacy of currently options in the pipeline.

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Section: Key Pointsmentioning

confidence: 99%

Gene therapy for age-related macular degeneration: potential, feasibility, and pitfalls

Berkowitz,

Finn

2024

Current Opinion in Ophthalmology

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Conversion to faricimab after prior anti-vascular endothelial growth factor therapy for persistent diabetic macular oedema

Durrani,

Momenaei,

Wakabayashi

et al. 2024

Br J Ophthalmol

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BackgroundTo assess the anatomical and functional outcomes in eyes with persistent diabetic macular oedema (pDME) on chronic anti-vascular endothelial growth factor therapy switched to intravitreal faricimab.MethodsPatients with pDME on chronic anti-vascular endothelial growth factor therapy that were switched to faricimab and received at least three injections at our institution between April 2022 and May 2023 were included in this study. Patients were excluded if they had complete response to previous treatment but were switched to extend treatment intervals if they had steroid or laser treatment for DME within 6 months prior to switch. Clinical and imaging data were extracted from the electronic medical record. Central foveal thickness (CFT) and Snellen visual acuity (VA) were obtained before and after three intravitreal faricimab injections. Generalised estimating equations were used to analyse the change in CFT and VA.ResultDuring the study period, 69 eyes of 53 patients met inclusion criteria. The mean age was 68.6±9.0 years. The mean number of injections prior to switch was 18.1±16.0. Pre-switch mean logarithm of the minimal angle of resolution VA was 0.40±0.30 (Snellen equivalent 20/50) and 0.38±0.27 (Snellen equivalent 20/48) after three faricimab injections (p=0.397). Mean CFT improved from 380±155 microns to 323±147 microns (p<0.001). No ophthalmic or systemic adverse events occurred during the study period.ConclusionsIntravitreal faricimab can improve anatomic outcomes while maintaining visual acuity in eyes with pDME previously treated with anti-VEGF therapy.

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Intraocular neutralizing antibodies against aflibercept in patients with age related macular degeneration

Cited by 2 publications

References 50 publications

Gene therapy for age-related macular degeneration: potential, feasibility, and pitfalls

Gene therapy for age-related macular degeneration: potential, feasibility, and pitfalls

Conversion to faricimab after prior anti-vascular endothelial growth factor therapy for persistent diabetic macular oedema

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